Sodium Bromide → HCID 59199432, compound

HRID 2089539Notes

Reaction equation

HRID 2089539 reaction equation
[CH:1]([O:4][C:5]([C:7]1[N:8]([CH:12]2[C:21]3[C:16](=[CH:17][C:18](OS(C(F)(F)F)(=O)=O)=[CH:19][CH:20]=3)[CH2:15][CH2:14][CH2:13]2)[CH:9]=[N:10][CH:11]=1)=[O:6])([CH3:3])[CH3:2].[CH:30]1(B(O)O)[CH2:32][CH2:31]1.[F-].[K+].[Br-].[Na+]>O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(C)C=CC=CC=1>[CH:1]([O:4][C:5]([C:7]1[N:8]([CH:12]2[C:21]3[C:16](=[CH:17][C:18]([CH:30]4[CH2:32][CH2:31]4)=[CH:19][CH:20]=3)[CH2:15][CH2:14][CH2:13]2)[CH:9]=[N:10][CH:11]=1)=[O:6])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 253881Sodium BromideHCID 522689Potassium FluorideHCID 2760897Cyclopropylboronic acidHCID 59199400HCID 59199400, compound

Product 1

HCID 59199432HCID 59199432, compound

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A flask is charged with 3-(6-trifluoromethanesulfonyloxy-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester (0.183 g, 0.426 mmol), which can be prepared as described in Example 48, cyclopropylboronic acid (0.091 g, 1.059 mmol), potassium fluoride (0.081 g, 1.39 mmol), sodium bromide (0.043 g, 0.423 mmol) and toluene (5 mL). Tetrakis(triphenylphosphine) palladium (0.015 g, 0.013 mmol) is added and the mixture is heated to 90° C. overnight. The reaction is cooled to room temperature, diluted with water and extracted with dichloromethane. The organic phase is dried over Na2SO4, filtered, and concentrated to give a residue, which is purified by silica gel chromatography (elution with hexanes-ethyl acetate mixtures) to give 3-(6-cyclopropyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester; MS: (ESI) m/z 325.2 (M+H)+. The HCl salt of the title compound can be prepared by dissolution in diethyl ether followed by treatment with an excess of 1N HCl in diethyl ether. The resulting heterogeneous solution is concentrated to furnish the HCl salt of 3-(6-cyclopropyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester; 1H NMR (400 MHz, MeOD) δ ppm 0.71-0.75 (m, 2 H), 1.00-1.05 (m, 2 H), 1.43 (d, J=6.3 Hz, 3 H), 1.46 (d, J=6.3 Hz, 3 H), 1.65-1.76 (m, 1 H), 1.87-1.98 (m, 2 H), 2.24-2.39 (m, 2 H), 2.87 (ddd, J=16.9, 9.3, 5.3 Hz, 1 H), 3.00 (dt, J=16.9, 5.0 Hz, 1 H), 5.34 (sept, J=6.3 Hz, 1 H), 6.51 (t, J=4.8 Hz, 1 H), 6.98 (dd, J=9.3, 1.2 Hz, 1 H), 7.03 (d, J=9.3 Hz, 2 H), 8.32 (d, J=1.5 Hz, 1 H), 8.51 (d, J=1.0 Hz, 1 H).

Workup

  1. customcan be prepared
  2. temperatureThe reaction is cooled to room temperature
  3. extractionextracted with dichloromethane
  4. dry with materialThe organic phase is dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a residue, which
  8. customis purified by silica gel chromatography (elution with hexanes-ethyl acetate mixtures)

Sources & evidence

ORD record
ord-c772ef42738345d1bec5e9014e6508d0
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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